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BACKGROUND: Eosinophilic solid and cystic (ESC) renal cell carcinoma (RCC), a unique and emerging subtype of RCC, has an indolent nature; in some rare instances, it may exhibit metastatic potential. Current cases are inadequate to precisely predict the clinical outcome of ESC RCC and determine treatment choices. CASE SUMMARY: Herein, we report two patients with ESC RCC. Patient 1 was a young woman with classical pathological characteristics. Patient 2 was a 52-year-old man with multifocal metastases, involving the pulmonary hilar and mediastinal lymph nodes, liver, brain, mesosternum, vertebra, rib, femur, and symphysis pubis. Awareness of ESC RCC, along with its characteristic architecture and immunophenotype, would contribute to making a definitive diagnosis, even on core biopsy samples. CONCLUSION: The discovery of ESC RCC molecular signatures may provide new therapeutic strategies in the future.
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The widespread use of silver nanoparticles (AgNPs) in commercial and industrial applications has led to their increased presence in the environment, raising concerns about their ecological and health impacts. This study pioneers an investigation into the chronic versus short-term acute toxicological impacts of differently coated AgNPs on zebrafish, with a novel focus on the thyroid-disrupting effects previously unexplored. The results showed that acute toxicity ranked from highest to lowest as AgNO3 (0.128 mg/L), PVP-AgNPs (1.294 mg/L), Citrate-AgNPs (6.984 mg/L), Uncoated-AgNPs (8.269 mg/L). For bioaccumulation, initial peaks were observed at 2 days, followed by fluctuations over time, with the eventual highest enrichment seen in Uncoated-AgNPs and Citrate-AgNPs at concentrations of 13 and 130 µg/L. Additionally, the four exposure groups showed a significant increase in T3 levels, which was 1.28-2.11 times higher than controls, and significant changes in thyroid peroxidase (TPO) and thyroglobulin (TG) content, indicating thyroid disruption. Gene expression analysis revealed distinct changes in the HPT axis-related genes, providing potential mechanisms underlying the thyroid toxicity induced by different AgNPs. The higher the Ag concentration in zebrafish, the stronger the thyroid disrupting effects, which in turn affected growth and development, in the order of Citrate-AgNPs, Uncoated-AgNPs > AgNO3, PVP-AgNPs. This research underscores the importance of considering nanoparticle coatings in risk assessments and offers insights into the mechanisms by which AgNPs affect aquatic organisms' endocrine systems, highlighting the need for careful nanotechnology use and the relevance of these findings for understanding environmental pollutants' role in thyroid disease.
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Nanopartículas del Metal , Plata , Glándula Tiroides , Contaminantes Químicos del Agua , Pez Cebra , Animales , Plata/toxicidad , Plata/química , Nanopartículas del Metal/toxicidad , Nanopartículas del Metal/química , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/metabolismo , Contaminantes Químicos del Agua/toxicidad , Bioacumulación , Tiroglobulina/metabolismoRESUMEN
BACKGROUND: Tanreqing injection (TRQ) has been employed in clinical practice as a treatment for dengue fever (DF). Nevertheless, the precise pharmacological mechanism underlying its efficacy remains elusive. METHOD: Network pharmacology, molecular docking, transcriptome sequencing, and experimental evaluation were employed to analyze and study the inhibitory potential of TRQ against dengue virus (DENV). RESULT: We found that TRQ inhibited the replication of DENV in human umbilical vein endothelial cells, Huh-7 cells, and Hep3B cells. In addition, TRQ prolonged the survival duration of AG129 mice infected with DF, decreased the viral load in serum and organs, and alleviated organ damage. Subsequently, ultra-high-performance liquid chromatography-tandem mass spectrometry analysis of TRQ was performed to identify 314 targets associated with 36 active compounds present in TRQ. Integration of multiple databases yielded 47 DF-related genes. Then, 15 hub targets of TRQ in DF were determined by calculating the network topology parameters (Degree). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that these pathways were primarily enriched in the processes of cytokine activation and leukocyte cross-endothelial migration, with significant enrichment of cell adhesion molecules. Molecular docking revealed favorable binding affinity between TRQ's key active compounds and the predicted hub targets. Transcriptome sequencing results showed TRQ's ability to restore the expression of vascular cell adhesion molecule-1 (VCAM-1) post-DENV infection. Finally, TRQ was found to modulate the immune status by regulating the nuclear factor kappa-B (NF-κB)- intercellular cell adhesion molecule-1 (ICAM-1)/VCAM-1 axis, as well as reduce immune cell alterations, inflammatory factor secretion, vascular permeability, and bleeding tendencies induced by DENV infection. CONCLUSION: Our research suggests that TRQ exerts therapeutic effects on DF by regulating the NF-κB-ICAM-1/VCAM-1 axis.
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Antivirales , Virus del Dengue , Dengue , Animales , Humanos , Ratones , Antivirales/farmacología , Dengue/tratamiento farmacológico , Virus del Dengue/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Células Endoteliales de la Vena Umbilical Humana , Molécula 1 de Adhesión Intercelular/metabolismo , Simulación del Acoplamiento Molecular , Farmacología en Red , FN-kappa B/metabolismo , Molécula 1 de Adhesión Celular Vascular/metabolismo , Replicación Viral/efectos de los fármacosRESUMEN
This study evaluated the impact of pulsed electric fields (PEFs) combined with three-phase partitioning (TPP) extraction methods on the physicochemical properties, functional properties, and structural characterization of the soluble dietary fiber (SDF) derived from peanut shells (PS). The findings of this study indicated that the application of a PEF-TPP treatment leads to a notable improvement in both the extraction yield and purity of SDF. Consequently, the PEF-TPP treatment resulted in the formation of more intricate and permeable structures, a decrease in molecular weight, and an increase in thermal stability compared to SDFs without TPP treatment. An analysis revealed that the PEF-TPP method resulted in an increase in the levels of arabinose and galacturonic acid, leading to enhanced antioxidant capacities. Specifically, the IC50 values were lower in SDFs which underwent PEF-TPP (4.42 for DPPH and 5.07 mg/mL for ABTS) compared to those precipitated with 40% alcohol (5.54 mg/mL for DPPH, 5.56 mg/mL for ABTS) and PEF75 (6.60 mg/mL for DPPH, 7.61 mg/mL for ABTS), respectively. Notably, the SDFs which underwent PEF-TPP demonstrated the highest water- and oil-holding capacity, swelling capacity, emulsifying activity, emulsion stability, glucose adsorption, pancreatic lipase inhibition, cholesterol adsorption, nitric ion adsorption capacity, and the least gelation concentration. Based on the synthesis scores obtained through PCA (0.536 > -0.030 > -0.33), which indicated that SDFs which underwent PEF-TPP exhibited the highest level of quality, the findings indicate that PEF-TPP exhibits potential and promise as a method for preparing SDFs.
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Antioxidantes , Arachis , Benzotiazoles , Ácidos Sulfónicos , Adsorción , Fibras de la DietaRESUMEN
Microplastics (MPs), which are prevalent and increasingly accumulating in aquatic environments. Other pollutants coexist with MPs in the water, such as pesticides, and may be carried or transferred to aquatic organisms, posing unpredictable ecological risks. This study sought to assess the adsorption of lambda-cyhalothrin (LCT) by virgin and aged polyethylene MPs (VPE and APE, respectively), and to examine their influence on LCT's toxicity in zebrafish, specifically regarding acute toxicity, oxidative stress, gut microbiota and immunity. The adsorption results showed that VPE and APE could adsorb LCT, with adsorption capacities of 34.4â¯mgâg-1 and 39.0â¯mgâg-1, respectively. Compared with LCT exposure alone, VPE and APE increased the acute toxicity of LCT to zebrafish. Additionally, exposure to LCT and PE-MPs alone can induce oxidative stress in the zebrafish gut, while combined exposure can exacerbate the oxidative stress response and intensify intestinal lipid peroxidation. Moreover, exposure to LCT or PE-MPs alone promotes inflammation, and combined exposure leads to downregulation of the myd88-nf-κb related gene expression, thus impacting intestinal immunity. Furthermore, exposure to APE increased LCT toxicity to zebrafish more than VPE. Meanwhile, exposure to PE-MPs and LCT alone or in combination has the potential to affect gut microbiota function and alter the abundance and diversity of the zebrafish gut flora. Collectively, the presence of PE-MPs may affect the toxicity of pesticides in zebrafish. The findings emphasize the importance of studying the interaction between MPs and pesticides in the aquatic environment.
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Microbioma Gastrointestinal , Microplásticos , Nitrilos , Estrés Oxidativo , Polietileno , Piretrinas , Contaminantes Químicos del Agua , Pez Cebra , Animales , Piretrinas/toxicidad , Nitrilos/toxicidad , Microplásticos/toxicidad , Contaminantes Químicos del Agua/toxicidad , Estrés Oxidativo/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , Polietileno/toxicidad , AdsorciónRESUMEN
BACKGROUND: Encephalitis caused by dengue virus (DENV) is considered a manifestation of severe dengue. Tanreqing injection (TRQ) is a well-known Chinese patented medicine, which has been used to treat brain-related disorders by inhibiting inflammation. Nevertheless, the effects of TRQ on DENV encephalitis have not been studied. The aim of this study was to evaluate the effects of TRQ on DENV encephalitis and to explore its potential mechanisms. METHODS: The cytotoxicity of TRQ was examined by MTT assay, and the anti-DENV activities of TRQ in BHK-21 baby hamster kidney fibroblast were evaluated through CCK-8 and plaque assays. The expression levels of NO, IL1B/IL-1ß, TNFα and IL6 were measured by qRTâPCR and ELISA in the BV2 murine microglial cell line. The inhibitory effects of TRQ on NLRP3 inflammasome activation in BV2 cells were examined by Western blotting, qRTâPCR and ELISA. The effects of TRQ on HT22 mouse hippocampal neuronal cells were examined by CCK-8 assay, morphology observation and flow cytometry. Moreover, a DENV-infected ICR suckling mouse model was developed to investigate the protective role of TRQ in vivo. RESULTS: TRQ decreased the release of NO, IL6, TNFα and IL1B from BV2 cells and inhibited the activation of NLRP3. The presence of the NLRP3 agonist nigericin reversed the anti-inflammatory activities of TRQ. Furthermore, TRQ inhibited the death of HT22 cells by decreasing IL1B in DENV-infected BV2 cells. In addition, TRQ significantly attenuated weight loss, reduced clinical scores and extended the survival in DENV-infected ICR suckling mice. Critically, TRQ ameliorated pathological changes in ICR suckling mice brain by inhibiting microglia and NLRP3 activation and decreasing the production of inflammatory factors and the number of dead neurons. CONCLUSION: TRQ exerts potent inhibitory effects on dengue encephalitis in vitro and in vivo by reducing DENV-2-induced microglial activation and subsequently decreasing the inflammatory response, thereby protecting neurons. These findings demonstrate the potential of TRQ in the treatment of dengue encephalitis.
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The interaction between pesticides and microplastics (MPs) can lead to changes in their mode of action and biological toxicity, creating substantial uncertainty in risk assessments. Succinate dehydrogenase inhibitor (SDHI) fungicides, a common fungicide type, are widely used. However, little is known about how penthiopyrad (PTH), a member of the SDHI fungicide group, interacts with polyethylene microplastics (PE-MPs). This study primarily investigates the individual and combined effects of virgin or aged PE-MPs and penthiopyrad on zebrafish (Danio rerio), including acute toxicity, bioaccumulation, tissue pathology, enzyme activities, gut microbiota, and gene expression. Short-term exposure revealed that PE-MPs enhance the acute toxicity of penthiopyrad. Long-term exposure demonstrated that PE-MPs, to some extent, enhance the accumulation of penthiopyrad in zebrafish, leading to increased oxidative stress injury in their intestines by the 7th day. Furthermore, exposure to penthiopyrad and/or PE-MPs did not result in histopathological damage to intestinal tissue but altered the gut flora at the phylum level. Regarding gene transcription, penthiopyrad exposure significantly modified the expression of pro-inflammatory genes in the zebrafish gut, with these effects being mitigated when VPE or APE was introduced. These findings offer a novel perspective on environmental behavior and underscore the importance of assessing the combined toxicity of PE-MPs and fungicides on organisms.
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Fungicidas Industriales , Pirazoles , Tiofenos , Contaminantes Químicos del Agua , Animales , Microplásticos/toxicidad , Microplásticos/metabolismo , Plásticos/toxicidad , Pez Cebra/metabolismo , Polietileno/toxicidad , Polietileno/metabolismo , Fungicidas Industriales/toxicidad , Fungicidas Industriales/metabolismo , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/metabolismoRESUMEN
BACKGROUND: Anaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma (LBCL) is an aggressive and rare variant of diffuse LBCL. Herein, we report an uncommon case of stage IE extranodal ALK-positive LBCL initially originating in the bulbar conjunctiva. CASE SUMMARY: A 63-year-old woman presented with a mass in the left bulbar conjunctiva that had persisted for six months, accompanied by swelling and pain that had persisted for 3 d. Eye examination revealed an 8 mm slightly elevated pink mass in the lower conjunctival sac of the left eye. Microscopically, the tumor was composed of large immunoblastic and plasmablastic large lymphoid cells with scattered anaplastic or multinucleated large cells. Immunophenotypically, the neoplastic cells were positive for ALK, CD10, CD138, Kappa, MUM1, BOB.1, OCT-2, CD4, CD45, EMA, CD79a, CD38, and AE1/AE3, and negative for CD20, PAX5, Lambda, BCL6, CD30 and all other T-cell antigens. The results of gene rearrangement tests showed monoclonal IGH/IGK/IGL and TCRD rearrangements. Fluorescence in situ hybridization studies did not reveal any BCL2, BCL6 or MYC rearrangements. Furthermore, Epstein-Barr virus was not detected by in situ hybridization in the lesions. Based on the histopathological and imaging examinations, the neoplasm was classified as stage IE ALK-positive LBCL. No further treatments were administered. At the 6, 15, and 21 mo postoperative follow-up visits, the patient was in good condition, without obvious discomfort. This case represents the first example of primary extranodal ALK-positive LBCL presenting as a bulbar conjunctival mass, which is extremely rare and shares morphological and immunohistochemical features with a variety of other neoplasms that can result in misdiagnosis. CONCLUSION: Awareness of the condition presented in this case report is necessary for early and accurate diagnosis and appropriate treatment.
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The application of chemotherapy drugs in tumor treatment has a long history, but the lack of selectivity of drugs often leads to serious side effects during chemotherapy. The natural anti-tumor ingredients derived from Chinese herbal medicine are attracting increased attention due to their diverse anti-tumor effects, abundant resources, and minimal side effects. An effective anti-tumor strategy may lie in the combination of these naturally derived anti-tumor ingredients with conventional chemotherapy drugs. This approach could potentially inhibit tumor growth and the development of drug resistance in tumor cells while reducing the adverse effects of chemotherapy drugs. This review provides a comprehensive overview of the combined therapy strategies integrating natural anti-tumor components from Chinese herbal medicine with chemotherapy drugs in current research. We primarily summarize various compounds in Chinese herbal medicine exhibiting natural anti-tumor activities and the relevant mechanisms in synergistic anti-tumor combination therapy. The focus of this paper is on underlining that this integrative approach, combining natural anti-tumor components of Chinese herbal medicine with chemotherapy drugs, presents a novel cancer treatment methodology, thereby providing new insights for future oncological research.
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OBJECTIVE: To explore the anti-inflammatory effects of ethyl lithospermate in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine-derived macrophages and zebrafish, and its underlying mechanisms. METHODS: 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide (MTT) assays were performed to investigate the toxicity of ethyl lithospermate at different concentrations (12.5-100 µ mol/L) in RAW 264.7 cells. The cells were stimulated with LPS (100 ng/mL) for 12 h to establish an inflammation model in vitro, the production of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor α (TNF-α) were assessed by enzyme linked immunosorbent assay (ELISA). Western blot was used to ascertain the protein expressions of signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa B (NF-κB) p65, phospho-STAT3 (p-STAT3, Tyr705), inhibitor of NF-κB (IκB) α, and phospho-I κB α (p-IκB α, Ser32), and confocal imaging was used to identify the nuclear translocation of NF-κB p65 and p-STAT3 (Tyr705). Additionally, the yolk sacs of zebrafish (3 days post fertilization) were injected with 2 nL LPS (0.5 mg/mL) to induce an inflammation model in vivo. Survival analysis, hematoxylin-eosin (HE) staining, observation of neutrophil migration, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to further study the anti-inflammatory effects of ethyl lithospermate and its probable mechanisms in vivo. RESULTS: The non-toxic concentrations of ethyl lithospermate have been found to range from 12.5 to 100 µ mol/L. Ethyl lithospermate inhibited the release of IL-6 and TNF-α(P<0.05 or P<0.01), decreased IκBα degradation and phosphorylation (P<0.05) as well as the nuclear translocation of NF-κB p65 and p-STAT3 (Tyr705) in LPS-induced RAW 264.7 cells (P<0.01). Ethyl lithospermate also decreased inflammatory cells infiltration and neutrophil migration while increasing the survival rate of LPS-stimulated zebrafish (P<0.05 or P<0.01). In addition, ethyl lithospermate also inhibited the mRNA expression levels of of IL-6, TNF-α, IκBα, STAT3, and NF-κB in LPS-stimulated zebrafish (P<0.01). CONCLUSION: Ethyl lithospermate exerts anti-Inflammatory effected by inhibiting the NF-κB and STAT3 signal pathways in RAW 264.7 macrophages and zebrafish.
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Lipopolisacáridos , FN-kappa B , Animales , Ratones , FN-kappa B/metabolismo , Células RAW 264.7 , Pez Cebra , Inhibidor NF-kappaB alfa/metabolismo , Interleucina-6/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Transcripción STAT3/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéuticoRESUMEN
BACKGROUND: Dengue virus (DENV) is a major public health threat. However, there are no specific therapeutic drugs for DENV. Many Chinese heat-cleaning formulas, such as Liang-Ge-San (LGS), have been frequently used in the virus-induced diseases. The antiviral effect of LGS has not been reported yet. PURPOSE: In this study, the effect of LGS on the inhibition of dengue virus serotype 2 (DENV-2) was investigated and the relevant mechanism was explored. METHODS: High-performance liquid chromatography was applied to analyze the chemical characterization of LGS. The in vitro antiviral activities of LGS against DENV-2 were evaluated by time-of-drug-addition assay. The binding of heat shock protein 70 (Hsp70) and envelope (E) protein or caveolin1 (Cav1) were analyzed by immunofluorescence and immunoprecipitation assays. Then the role of Cav1 in the anti-DENV-2 effects of LGS was further examined. DENV-2 infected Institute of Cancer Research suckling mice (n = 10) and AG129 mice (n = 8) were used to examine the protective effects of LGS. RESULTS: It was found that geniposide, liquiritin, forsythenside A, forsythin, baicalin, baicalein, rhein, and emodin maybe the characteristic components of LGS. LGS inhibited the early stage of DENV-2 infection, decreased the expression levels of viral E and non-structural protein 1 (NS1) proteins. LGS also reduced E protein and Hsp70 binding and attenuated the translocation of Hsp70 from cytoplasm to the cell membrane. Moreover, LGS decreased the binding of Hsp70 to Cav1. Further study showed that the overexpression of Cav1 reversed LGS-mediated E protein and Hsp70 inhibition in the plasma membrane. In the in vivo study, LGS was highly effective in prolonging the survival time, reducing viral loads. CONCLUSION: This work demonstrates for the first time that LGS exerts anti-DENV-2 activity in vitro and in vivo. LGS decreases DENV-2-stimulated cytoplasmic Hsp70 translocation into the plasma membrane by Cav1 inhibition, thereby inhibiting the early stage of virus infection. These findings indicate that LGS may be a candidate for the treatment of DENV.
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Virus del Dengue , Dengue , Animales , Ratones , Dengue/tratamiento farmacológico , Proteínas HSP70 de Choque Térmico , Serogrupo , Membrana Celular , Antivirales/farmacología , Antivirales/uso terapéutico , Citoplasma/metabolismoRESUMEN
The co-exposure of microplastics (MPs) and other contaminants has aroused extensive attention, but the combined impacts of MPs and pesticides remain poorly understood. Acetochlor (ACT), a widely used chloroacetamide herbicide, has raised concerns for its potential bio-adverse effects. This study evaluated the influences of polyethylene microplastics (PE-MPs) for acute toxicity, bioaccumulation, and intestinal toxicity in zebrafish to ACT. We found that PE-MPs significantly enhanced ACT acute toxicity. Also, PE-MPs increased the accumulation of ACT in zebrafish and aggravate the oxidative stress damage of ACT in intestines. Exposure to PE-MPs or/and ACT causes mild damage to the gut tissue of zebrafish and altered gut microbial composition. In terms of gene transcription, ACT exposure triggered a significant increase in inflammatory response-related gene expressions in the intestines, while some pro-inflammatory factors were found to be inhibited by PE-MPs. This study provides a new perspective on the fate of MPs in the environment and on the assessment of the combined effects of MPs and pesticides on organisms.
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Microplásticos , Contaminantes Químicos del Agua , Animales , Microplásticos/toxicidad , Microplásticos/metabolismo , Polietileno/toxicidad , Polietileno/metabolismo , Plásticos/metabolismo , Pez Cebra/metabolismo , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/metabolismoRESUMEN
BACKGROUND: At present, about half of the world's population is at risk of being infected with dengue virus (DENV). However, there are no specific drugs to prevent or treat DENV infection. Glycyrrhizae Radix et Rhizome, a well-known traditional Chinese medicine, performs multiple pharmacological activities, including exerting antiviral effects. The aim of this study was to investigate the anti-DENV effects of n-butanol extract from Glycyrrhizae Radix et Rhizome (GRE). METHODS: Compounds analysis of GRE was conducted via ultra-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS). The antiviral activities of GRE were determined by the CCK-8 assay, plaque assay, qRT-PCR, Western blotting, and the immunofluorescence assay. The DENV-infected suckling mice model was constructed to explore the antiviral effects of GRE in vivo. RESULTS: Four components in GRE were analyzed by UHPLC-MS/MS, including glycyrrhizic acid, glycyrrhetnic acid, liquiritigenin, and isoliquiritigenin. GRE inhibited the attachment process of the virus replication cycle and reduced the expression of the E protein in cell models. In the in vivo study, GRE significantly relieved clinical symptoms and prolong survival duration. GRE also significantly decreased viremia, reduced the viral load in multiple organs, and inhibited the release of pro-inflammatory cytokines in DENV-infected suckling mice. CONCLUSIONS: GRE exhibited significant inhibitory activities in the adsorption stage of the DENV-2 replication cycle by targeting the envelope protein. Thus, GRE might be a promising candidate for the treatment of DENV infection.
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Degradable plastics are gradually regarded as alternatives of conventional, synthetic organic polymers to reduce the plastics or microplastics (MPs) pollution; however, the reports upon environmental risk of degradable plastics are still limited. In order to evaluate the potential vector effect of biodegradable MPs on coexisting contaminants, sorption of atrazine onto pristine and ultraviolet-aged (UV) polybutylene adipate co-terephthalate (PBAT) MPs and polybutylene succinate co-terephthalate (PBST) MPs were investigated. The results showed that, UV aging led to more wrinkles and cracks on the surface, increased homogeneous chains proportion, enhanced hydrophobicity, and enlarged crystallinity of both MPs. The sorption kinetics of atrazine to MPs fitted well into pseudo-first-order (R2 = 0.809-0.996) and pseudo-second-order (R2 = 0.889-0.994) models. In the concentration range of 0.5-25 mg L-1, the sorption isotherm fitted into linear (R2 = 0.967-0.996) and Freundlich model (R2 = 0.972-0.997), indicating that the absorption partitioning was the dominant sorption mechanism. The partition coefficient (Kd) of atrazine to PBAT- MPs (40.11-66.01 L kg-1) was higher than that of PBST- MPs (34.34-57.96 L kg-1), and the Kd values of both MPs declined for aged MPs. The specific surface area, hydrophobicity, polarity and crystallinity of MPs jointly interpreted the changing sorption capacity of the MPs. In the present study, both aged PBAT- and aged PBST- MPs exhibited lower vector potential to atrazine than pristine MPs, suggesting reduced risk of being a pollutant carrier, which is of great significance for the development of biodegradable plastics.
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Atrazina , Contaminantes Ambientales , Contaminantes Químicos del Agua , Microplásticos , Plásticos , Adsorción , Contaminantes Químicos del Agua/análisisRESUMEN
BACKGROUND: Licorice (Glycyrrhiza uralensis Fisch.), a well-known traditional medicine, is traditionally used for the treatment of respiratory disorders, such as cough, sore throat, asthma and bronchitis. We aim to investigate the effects of liquiritin (LQ), the main bioactive compound in licorice against acute lung injury (ALI) and explore the potential mechanism. METHODS: Lipopolysaccharide (LPS) was used to induce inflammation in RAW264.7 cells and zebrafish. Intratracheal instillation of 3 mg/kg of LPS was used for induction an ALI mice model. The concentrations of IL-6 and TNF-α were tested using the enzyme linked immunosorbent assay. Western blot analysis was used to detect the expression of JNK/Nur77/c-Jun related proteins. Protein levels in bronchoalveolar lavage fluid (BALF) was measured by BCA protein assay. The effect of JNK on Nur77 transcriptional activity was determined by luciferase reporter assay, while electrophoretic mobility shift assay was used to examine the c-Jun DNA binding activity. RESULTS: LQ has significant anti-inflammatory effects in zebrafish and RAW264.7 cells. LQ inhibited the expression levels of p-JNK (Thr183/Tyr185), p-Nur77 (Ser351) and p-c-Jun (Ser63), while elevated the Nur77 expression level. Inhibition of JNK by a specific inhibitor or small interfering RNA enhanced the regulatory effect of LQ on Nur77/c-Jun, while JNK agonist abrogated LQ-mediated effects. Moreover, Nur77-luciferase reporter activity was suppressed after JNK overexpression. The effects of LQ on the expression level of c-Jun and the binding activity of c-Jun with DNA were attenuated after Nur77 siRNA treatment. LQ significantly ameliorated LPS-induced ALI with the reduction of lung water content and BALF protein content, the downregulation of TNF-α and IL-6 levels in lung BALF and the suppression of JNK/Nur77/c-Jun signaling, which can be reversed by a specific JNK agonist. CONCLUSION: Our results indicated that LQ exerts significant protective effects against LPS-induced inflammation both in vivo and in vitro via suppressing the activation of JNK, and consequently inhibiting the Nur77/c-Jun signaling pathway. Our study suggests that LQ may be a potential therapeutic candidate for ALI and inflammatory disorders.
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OBJECTIVE: Mid- to late-Holocene large-scale population migration profoundly impacted the interaction of ethnic groups and cultures across Eurasia, notably in Central Asia. However, due to a lack of thorough historical documents, distinctive burial items, and human remains, the process of population migration during this historical era in the area is still unclear. Using an interdisciplinary approach at the Lafuqueke (LFQK) cemetery, this study investigates the spatiotemporal processes and explores the factors that influenced human migration in the eastern Tianshan Mountains between the 7th and 12th centuries. MATERIALS AND METHODS: In this study, tooth enamel from 56 human remains found in the LFQK cemetery in Hami Basin, eastern Tianshan Mountains, is examined for strontium and lead isotopes. RESULTS: The early, middle, and late phases of migration might potentially be represented by a three-phase migration model, according to the isotopic study. The highest proportion of the early phase (ca. 7th-mid 7th century) comprised non-locals (54.55%), although this percentage decreased in the middle phase (mid 7th-mid 8th centuries, 30.77%). After the 10th century, the proportion of non-locals again fell (16.13%). CONCLUSION: In this study, the interdisciplinary approach was employed to propose a new model for the diachronic changes that accompanied human migration and cultural interaction in the eastern Tianshan Mountains and identified geopolitics as a significant factor influencing the migratory behavior of LFQK population in this region between the 7th and 12th centuries.
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Restos Mortales , Isótopos , Humanos , Asia Central , Cementerios , Migración HumanaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Dengue virus (DENV) infection is a global public health issue without effective therapeutic interventions. Chinese medicine with heat-clearing and detoxifying properties has been frequently used in the treatment of viral infection. Ampelopsis Radix (AR) is a traditional Chinese medicine for clearing heat and detoxification that has been widely used in the prevention and treatment of infectious diseases. However, no studies on the effects of AR against viral infection have been reported, thus far. AIM OF THE STUDY: To explore the anti-DENV activities of the fraction (AR-1) obtained from AR both in vitro and in vivo. MATERIALS AND METHODS: The chemical composition of AR-1 was identified by liquid chromatography-tandem MS (LCâMS/MS). The antiviral activities of AR-1 were studied in baby hamster kidney fibroblast BHK-21 cells, ICR suckling mice and induction of interferon α/ß (IFN-α/ß) and IFN-γ R-/- (AG129) mice. RESULTS: Based on LCâMS/MS analysis, 60 compounds (including flavonoids, phenols, anthraquinones, alkaloids and other types) were tentatively characterized from AR-1. AR-1 inhibited the cytopathic effect, the production of progeny virus and the synthesis of viral RNA and proteins by blocking DENV-2 binding to BHK-21 cells. Moreover, AR-1 significantly attenuated weight loss, decreased clinical scores and prolonged the survival of DENV-infected ICR suckling mice. Critically, the viral load in blood, brain and kidney tissues and the pathological changes in brain were remarkably alleviated after AR-1 treatment. Further study on AG129 mice showed that AR-1 obviously improved the clinical manifestations and survival rate, reduced viremia, attenuated gastric distension and relieved the pathological lesions caused by DENV. CONCLUSIONS: In summary, this is the first report that AR-1 exhibits anti-DENV effects both in vitro and in vivo, which suggests that AR-1 may be developed as a therapeutic candidate against DENV infection.
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Ampelopsis , Animales , Ratones , Cromatografía Liquida , Ratones Endogámicos ICR , Espectrometría de Masas en Tándem , Antivirales/farmacología , Antivirales/uso terapéutico , Replicación ViralRESUMEN
OBJECTIVE: A set of cardiac MRI short-axis image dataset is constructed, and an automatic segmentation based on an improved SegNet model is developed to evaluate its performance based on deep learning techniques. METHODS: The Affiliated Hospital of Qingdao University collected 1354 cardiac MRI between 2019 and 2022, and the dataset was divided into four categories: for the diagnosis of cardiac hypertrophy and myocardial infraction and normal control group by manual annotation to establish a cardiac MRI library. On the basis, the training set, validation set and test set were separated. SegNet is a classical deep learning segmentation network, which borrows part of the classical convolutional neural network, that pixelates the region of an object in an image division of levels. Its implementation consists of a convolutional neural network. Aiming at the problems of low accuracy and poor generalization ability of current deep learning frameworks in medical image segmentation, this paper proposes a semantic segmentation method based on deep separable convolutional network to improve the SegNet model, and trains the data set. Tensorflow framework was used to train the model and the experiment detection achieves good results. RESULTS: In the validation experiment, the sensitivity and specificity of the improved SegNet model in the segmentation of left ventricular MRI were 0.889, 0.965, Dice coefficient was 0.878, Jaccard coefficient was 0.955, and Hausdorff distance was 10.163 mm, showing good segmentation effect. CONCLUSION: The segmentation accuracy of the deep learning model developed in this paper can meet the requirements of most clinical medicine applications, and provides technical support for left ventricular identification in cardiac MRI.
Asunto(s)
Procesamiento de Imagen Asistido por Computador , Infarto del Miocardio , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Redes Neurales de la Computación , Imagen por Resonancia Magnética , Infarto del Miocardio/diagnóstico por imagen , Cardiomegalia/diagnóstico por imagenRESUMEN
Background: Hepatocellular carcinoma (HCC) is characterized by poor diagnosis and high mortality. Novel and efficient therapeutic agents are urgently needed for the treatment. Hedyotis diffusa Willd (HDW) is used to treat cancers, especially HCC in China. Purpose: The study aimed to identify the main anti-HCC extract in HDW and to explore the mechanism of the active extract. Materials and Methods: The high-performance liquid chromatography-quadrupole-time of flight mass spectrometry (HPLC-QTOF-MS) method was used for the simultaneous determination of main compounds in the ethyl acetate fraction of HDW (EHDW). The toxicity test of different HDW fractions was carried out on larvae at 2 day-post-fertilization (dpf) for 72 h. The in vivo anti-HCC effect of different HDW fractions was evaluated on a zebrafish tumor model by immersion administration. The antiproliferative effect of HDW fractions was determined with MTT assay, as well as hematoxylin and eosin (HE) staining assay. Hoechst 33258 staining was used to observe changes in nucleus morphology. Flow cytometry analysis was used to investigate apoptosis induction. Western blot analysis was used to examine apoptosis-related proteins, and key proteins in JNK/Nur77 signaling pathway. SP600125 was served to validate the apoptotic mechanism. Results: EHDW showed the strongest tumor cell growth inhibitory effect on zebrafish tumor model. Further study revealed that EHDW induced apoptosis in zebrafish tumor model and in cultured Hep3B cells. Meanwhile, it has been shown that the levels of BCL2-associated X (Bax), cytochrome c (cyto c), cleaved-caspase 3, and poly-ADP-ribose polymerase (PARP) cells were upregulated. In contrast, the level of antiapoptotic B cell lymphoma-2 (Bcl-2) was downregulated in Hep3B cells. Additionally, EHDW activated JNK/Nur77 pathway by increasing the levels of p-JNK(Thr183/Tyr185) and p-Nur77(Ser351). Further study showed that blockage of JNK by SP600125 reversed EHDW-induced JNK/Nur77 pathway and the downstream apoptotic proteins. Conclusion: In conclusion, EHDW exerted the anti-HCC effect, which may be attributed to the activation of JNK/Nur77 pathway. This study supported the rationale of HDW as an HCC therapeutic agent.